CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse.

Published

Journal Article

How T cells respond with extraordinary sensitivity to minute amounts of agonist peptide and major histocompatibility complex (pMHC) molecules on the surface of antigen-presenting cells bearing large numbers of endogenous pMHC molecules is not understood. Here we present evidence that CD4 affects the responsiveness of T helper cells by controlling spatial localization of the tyrosine kinase Lck in the synapse. This finding, as well as further in silico and in vitro experiments, led us to develop a molecular model in which endogenous and agonist pMHC molecules act cooperatively to amplify T cell receptor signaling. At the same time, activation due to endogenous pMHC molecules alone is inhibited. A key feature is that the binding of agonist pMHC molecules to the T cell receptor results in CD4-mediated spatial localization of Lck, which in turn enables endogenous pMHC molecules to trigger many T cell receptors. We also discuss broader implications for T cell biology, including thymic selection, diversity of the repertoire of self pMHC molecules and serial triggering.

Full Text

Duke Authors

Cited Authors

  • Li, Q-J; Dinner, AR; Qi, S; Irvine, DJ; Huppa, JB; Davis, MM; Chakraborty, AK

Published Date

  • August 2004

Published In

Volume / Issue

  • 5 / 8

Start / End Page

  • 791 - 799

PubMed ID

  • 15247914

Pubmed Central ID

  • 15247914

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni1095

Language

  • eng

Conference Location

  • United States